Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/25527
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dc.contributor.authorRato, Luis-
dc.contributor.authorDuarte, Ana I.-
dc.contributor.authorTomás, Gonçalo D.-
dc.contributor.authorSantos, M. S.-
dc.contributor.authorMoreira, Paula I.-
dc.contributor.authorSocorro, Silvia-
dc.contributor.authorCavaco, José E.-
dc.contributor.authorAlves, Marco G.-
dc.contributor.authorOliveira, Pedro F.-
dc.date.accessioned2014-04-09T11:55:14Z-
dc.date.available2014-04-09T11:55:14Z-
dc.date.issued2014-
dc.identifier.urihttps://hdl.handle.net/10316/25527-
dc.description.abstractPre-diabetes, a risk factor for type 2 diabetes development, leads to metabolic changes at testicular level. Peroxisome proliferator-activated receptor γ coactivator 1α(PGC-1α) and Sirtuin 3 (Sirt3) are pivotal inmitochondrial function. We hypothesized that pre-diabetes disrupts testicular PGC-1α/Sirt3 axis, compromising testicular mitochondrial function. Using a high-energy-diet induced pre-diabetic rat model, we evaluated testicular levels of PGC-1α and its downstream targets, nuclear respiratory factors 1 (NRF-1) and 2 (NRF-2),mitochondrial transcription factor A (TFAM) and Sirt3.We also assessedmitochondrial DNA (mtDNA) content, mitochondrial function, energy levels and oxidative stress parameters. Protein levels were quantified by Western Blot, mtDNA contentwas determined by qPCR.Mitochondrial complex activity and oxidative stress parameterswere spectrophotometrically evaluated. Adenine nucleotide levels, adenosine and its metabolites (inosine and hypoxanthine) were determined by reverse-phase HPLC. Pre-diabetic rats showed increased blood glucose levels and impaired glucose tolerance. Both testicular PGC-1α and Sirt3 levels were decreased. NRF-1, NRF-2 and TFAM were not altered. Testicular mtDNA content was decreased. Mitochondrial complex I activity was increased, whereas mitochondrial complex III activity was decreased. Adenylate energy charge was decreased in pre-diabetic rats, as were ATP and ADP levels. Conversely, AMP levels were increased, evidencing a decreased ATP/AMP ratio. Concerning to oxidative stress pre-diabetes decreased testicular antioxidant capacity and increased lipid and protein oxidation. In sum, pre-diabetes compromises testicular mitochondrial function by repressing PGC-1α/Sirt3 axis and mtDNA copy number, declining respiratory capacity and increasing oxidative stress. This study gives newinsights into overall testicular bioenergetics at this prodromal stage of disease.por
dc.description.sponsorshipThis work was supported by the Portuguese “Fundação para a Ciência e a Tecnologia”—FCT, co-funded by FEDER via Programa Operacional Factores de Competitividade—COMPETE/QREN (PTDC/ QUI-BIQ/121446/2010 and PEst-C/SAU/UI0709/2011). L. Rato (SFRH/ BD/72733/2010), A. I. Duarte (SFRH/BPD/26872/2006) and M. G. Alves (SFRH/BPD/80451/2011) were financed by FCT and European Social Fund. P. F. Oliveira was financed by FCT through FSE and POPH funds (Programa Ciência 2008).por
dc.language.isoengpor
dc.publisherElsevier B.V.por
dc.rightsopenAccesspor
dc.subjectHigh-energy dietpor
dc.subjectMitochondriapor
dc.subjectPGC-1α/Sirt3 axispor
dc.subjectPre-diabetespor
dc.subjectTesticular bioenergeticspor
dc.titlePre-diabetes alters testicular PGC1-α/SIRT3 axis modulating mitochondrial bioenergetics and oxidative stresspor
dc.typearticlepor
degois.publication.firstPage335por
degois.publication.lastPage344por
degois.publication.issue3por
degois.publication.titleBiochimica et Biophysica Actapor
dc.relation.publisherversionhttp://www.sciencedirect.com/science/article/pii/S0005272813002235#por
dc.peerreviewedYespor
dc.identifier.doi10.1016/j.bbabio.2013.12.008-
degois.publication.volume1837por
item.languageiso639-1en-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.fulltextCom Texto completo-
item.openairetypearticle-
item.grantfulltextopen-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.orcid0000-0002-6881-9392-
crisitem.author.orcid0000-0001-5177-6747-
Appears in Collections:FCTUC Ciências da Vida - Artigos em Revistas Internacionais
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